Mapping the Genetic Landscape of Human Cells.
Mapping the Genetic Landscape of Human Cells.
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DOI：
10.1016/j.cell.2018.06.010
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发表时间：
2018-08-09
期刊：
影响因子：
64.5
通讯作者：
Gilbert LA
中科院分区：
文献类型：
--
作者：
Horlbeck MA;Xu A;Wang M;Bennett NK;Park CY;Bogdanoff D;Adamson B;Chow ED;Kampmann M;Peterson TR;Nakamura K;Fischbach MA;Weissman JS;Gilbert LA
Seminal yeast studies established the value of comprehensively mapping genetic interactions (GIs) for inferring gene function. Efforts in human cells using focused gene sets underscore the utility of this approach, but the feasibility of generating large-scale, diverse human GI maps remains unresolved. We developed a CRISPR interference platform for large-scale quantitative mapping of human GIs. We systematically perturbed 222,784 gene pairs in two cancer cell lines. The resulting maps cluster functionally related genes, assigning function to poorly characterized genes, including TMEM261, a new electron transport chain component. Individual GIs pinpoint unexpected relationships between pathways, exemplified by a specific cholesterol biosynthesis intermediate whose accumulation induces deoxynucleotide depletion, causing replicative DNA damage and a synthetic-lethal interaction with the ATR/9-1-1 DNA repair pathway. Our map provides a broad resource, establishes GI maps as a high-resolution tool for dissecting gene function, and serves as a blueprint for mapping the genetic landscape of human cells. A large-scale genetic interaction map in human cells reveals unexpected interdependencies between core pathways and exposes potential combination therapies for cancer
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DOI：
10.1126/science.aah7111
发表时间：
2017-01-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Liu SJ;Horlbeck MA;Cho SW;Birk HS;Malatesta M;He D;Attenello FJ;Villalta JE;Cho MY;Chen Y;Mandegar MA;Olvera MP;Gilbert LA;Conklin BR;Chang HY;Weissman JS;Lim DA
通讯作者：
Lim DA
影响因子：
64.5
作者：
Frost A;Elgort MG;Brandman O;Ives C;Collins SR;Miller-Vedam L;Weibezahn J;Hein MY;Poser I;Mann M;Hyman AA;Weissman JS
通讯作者：
Weissman JS
影响因子：
4.5
作者：
Babu M;Arnold R;Bundalovic-Torma C;Gagarinova A;Wong KS;Kumar A;Stewart G;Samanfar B;Aoki H;Wagih O;Vlasblom J;Phanse S;Lad K;Yeou Hsiung Yu A;Graham C;Jin K;Brown E;Golshani A;Kim P;Moreno-Hagelsieb G;Greenblatt J;Houry WA;Parkinson J;Emili A
通讯作者：
Emili A
影响因子：
2.9
作者：
Cerqueira, Nuno M. F. S. A.;Oliveira, Eduardo F.;Fernandes, P. A.
通讯作者：
Fernandes, P. A.
影响因子：
7.7
作者：
Horlbeck, Max A.;Witkowsky, Lea B.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.